title: GLP-1 and exendin-4 can reverse hyperlipidic-related osteopenia.
abstract: Increased fat mass contributes to bone deterioration. Glucagon-like peptide 1 (GLP-1) and its related peptide exendin 1-39 amide (Ex-4), two lipid-lowering peptides, exert osteogenic effects in diabetic states. We examined the actions of 3-day administration of GLP-1 or Ex-4 on bone remodeling markers and on bone mass and structure in hyperlipidic (HL) and hypercaloric rats. Wistar rats on a hyperlipidemic diet for 35 days were subcutaneously administered GLP-1 (0.86  nmol/kg per h), Ex-4 (0.1  nmol/kg per h), or saline (control) by continuous infusion for 3 days. After killing, tibiae were removed for total RNA and protein isolation, as well as femurs and L1-L4 vertebrae for bone mass and quality assessment. Body weight and plasma insulin were unaltered in HL rats, which showed osteopenia (by dual-energy X-ray absorptiometry), associated with hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. GLP-1 or Ex-4 administration decreased the levels of glucose, triglycerides, and total cholesterol in plasma but increased osteocalcin (OC) gene expression and the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio - at the expense of an augmented OPG - above corresponding control values in the tibia. Each tested peptide similarly reversed the decreased femoral and vertebral bone mass in these rats, whereas the deteriorated trabecular structure in the vertebrae improved associated with normalization of bone remodeling. These findings demonstrate that GLP-1 and Ex-4 are similarly efficient in reversing the bone alterations in this HL rat model, which has proven to be useful for studying the fat-bone relationships.
authors.affiliation: Department of Metabolism, Nutrition and Hormones Bone and Mineral Metabolism Laboratory, Instituto de Investigación Sanitaria (IIS)-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Nuche-Berenguer
authors.forename: Daniel
authors.initials: D
authors.lastname: Lozano
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Rojas
authors.forename: Paola
authors.initials: P
authors.lastname: Moreno
authors.forename: María L
authors.initials: ML
authors.lastname: Mariñoso
authors.forename: Pedro
authors.initials: P
authors.lastname: Esbrit
authors.forename: María L
authors.initials: ML
authors.lastname: Villanueva-Peñacarrillo
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D054795:Incretins / Q000494:pharmacology / Q000627:therapeutic use*; D008159:Lumbar Vertebrae / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide